{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:51:59Z","timestamp":1777589519356,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T00:00:00Z","timestamp":1526860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003968","name":"Iran National Science Foundation","doi-asserted-by":"publisher","award":["95822933"],"award-info":[{"award-number":["95822933"]}],"id":[{"id":"10.13039\/501100003968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Resistance to antimonials is a fundamental determinant of treatment failure in anthroponotic cutaneous leishmaniasis (<jats:styled-content style=\"fixed-case\">ACL<\/jats:styled-content>). Detection of reliable molecular markers to distinguish unresponsive and responsive parasites is critical for consolidating strategies to monitor drug efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed the expression of five major antimony resistance\u2010associated genes that is aquaglyceroporin1 (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>1), <jats:italic>\u03b3<\/jats:italic>\u2010glutamylcysteine synthetase (<jats:italic>\u03b3<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">GCS<\/jats:styled-content>), multidrug resistance protein A (<jats:styled-content style=\"fixed-case\">MRPA<\/jats:styled-content>), trypanothione reductase (<jats:styled-content style=\"fixed-case\">TR<\/jats:styled-content>) and thiol\u2010dependent reductase 1 (<jats:styled-content style=\"fixed-case\">TDR<\/jats:styled-content>1), in unresponsive and responsive <jats:italic>Leishmania tropica<\/jats:italic> field isolates by quantitative real\u2010time <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> in comparison with sensitive and resistant reference strains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene expression analysis showed the down\u2010regulation of <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>1, <jats:italic>\u03b3<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">GCS<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TDR<\/jats:styled-content>1 by a factor of 1.9, 1.7 and 3.55, respectively, in unresponsive isolates <jats:italic>vs<\/jats:italic>. responsive ones. The average <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression level of <jats:styled-content style=\"fixed-case\">MRPA<\/jats:styled-content> increased by a factor of 1.9 in the unresponsive group. Isolates exhibited a strong positive linear correlation between gene expression of <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>1 and <jats:italic>\u03b3<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">GCS<\/jats:styled-content>. A negative correlation between the <jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>1 and <jats:italic>\u03b3<\/jats:italic>\u2010<jats:styled-content style=\"fixed-case\">GCS<\/jats:styled-content> expression level and lesion duration in responsive patients indicated the potential role in diagnosing drug\u2010unresponsive parasites in endemic areas of <jats:styled-content style=\"fixed-case\">ACL<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In cases of inconclusive outcomes of resistance tests in clinical isolates, expression analysis of a set of influential genes can be beneficial to identify distinctive biomarkers between antimony\u2010unresponsive and responsive parasites.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tmi.13062","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T20:43:25Z","timestamp":1525121005000},"page":"622-633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Unresponsiveness to meglumine antimoniate in anthroponotic cutaneous leishmaniasis field isolates: analysis of resistance biomarkers by gene expression profiling"],"prefix":"10.1111","volume":"23","author":[{"given":"Razieh Tavakoli","family":"Oliaee","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology and Mycology Kerman University of Medical Sciences Kerman Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iraj","family":"Sharifi","sequence":"additional","affiliation":[{"name":"Leishmaniasis Research Center Kerman University of Medical Sciences Kerman 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